Functional Polymorphism in the Interleukin-6 and Interleukin-10 Genes in Patients with Paranoid Schizophrenia —A Case-Control Study

Abstract

Schizophrenia is a multifactorial disease with changes in immunological system. Such changes are the result of cytokine-level disturbances connected with cytokine gene polymorphisms. However, research about cytokine gene polymorphisms in schizophrenia has been surprisingly limited and ambiguous. The aim of the study was to identify whether polymorphisms of interleukin (IL)-6 and IL-10 are risk factors for the development of paranoid schizophrenia in case-control study. IL-6 (-174G/C; rs 1800795) and IL-10 (-1082G/A; rs 1800896) promoter polymorphisms in patients with paranoid schizophrenia and healthy individuals were genotyped using polymerase chain reaction-restriction fragment length polymorphism method. Differences in IL-6 and IL-10 promoter haplotypes may play an important role in determining the transcription level for IL-6 and IL-10 genes in schizophrenic patients. The presence of allele C at position -174 of IL-6 promoter sequence may correlate with increasing risk of paranoid schizophrenia in the Polish population, but research on a broadened group of people is needed. The presence of allele G at position -1082 of IL-10 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population. The coexistence of genotype GG at position -1082 of IL-10 promoter sequence and genotype GC at position -174 of IL-6 promoter sequence correlates with increasing risk of paranoid schizophrenia in the Polish population.

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

“…Interestingly, both polymorphisms have previously been associated with the disease. [60][61][62] Moreover, IL6 rs1800795, located in the promoter region, has been associated with increased IL-6 blood levels 61 and with reduced hippocampal volume in antipsychotic-naive patients with schizophrenia. 63 We also propose a predictive genetic model for schizophrenia risk that includes the MyD88, IL6 and IL1B genes, as well as another 2 key genes in the intracellular signalling of the TLR4 pathway: NFKB1 and IRAK.…”

Prenatal infection, maternal immune activation, and risk for schizophrenia

“…The MHC locus encodes several genes that are involved in the innate and adaptive immune systems, and as noted above, MHC-1 is known to be important for synaptic pruning during neural development [64]. Additionally, in candidate gene studies, polymorphisms in several other immune signaling proteins including interleukins-2, 3, 4, 6 and 10 as well as nuclear factor κ-light-chain-enhancer of activated B cells (NFκB), have been associated with increased risk of developing schizophrenia [70–74]. These studies suggest that an immune-related basis to schizophrenia might be genetically, as well as environmentally, encoded.…”

The Interaction of Polymorphisms of IL10 and DBH Was Associated with General Symptoms of PANSS with TD in Chinese Han Schizophrenic Patients

“…Level of IL10 increasing in the cerebrospinal fluid of schizophrenics has been described before [7], [8]; a previous study has mentioned that a strong relationship between an increased IL10 level in cerebrospinal fluid and negative symptoms of schizophrenia was observed [9]. Some polymorphisms on IL10 gene are associated with susceptibility to the development of schizophrenia [10]–[12]. The C to A nucleotide exchange of rs1800872 gives rise to increased IL10 gene promoter activity, suggesting its role as a repressor element of the C allele [13].…”